Background: Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis. Methods: WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint. Results/Conclusions: At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids downregulated muscle proteins and upregulated certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy.

EMM has been a consultant to Amgen, AstraZeneca, Cytokinetics, Pfizer, Tenaya Therapeutics, and is a founder of Ikaika Therapeutics. ARD is CSO of Ikaika Therapeutics. The other authors have declared that no conflict of interest exists.

NCT04054375

Supported by the Kurt+Peter Foundation, National Institutes of Health AR052646, NS047726, NS127383, and HL061322 and Parent Project Muscular Dystrophy. We thank Dr. Todd Parrish and the Center for Translational Imaging at Northwestern.

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